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Review
. 2003 Jan;202(1):59-68.
doi: 10.1046/j.1469-7580.2003.00139.x.

The formation of skeletal muscle: from somite to limb

Margaret Buckingham  1 , Lola Bajard, Ted Chang, Philippe Daubas, Juliette Hadchouel, Sigolène Meilhac, Didier Montarras, Didier Rocancourt, Frédéric Relaix
Affiliations
Review

The formation of skeletal muscle: from somite to limb

Margaret Buckingham et al. J Anat. 2003 Jan.

Abstract

During embryogenesis, skeletal muscle forms in the vertebrate limb from progenitor cells originating in the somites. These cells delaminate from the hypaxial edge of the dorsal part of the somite, the dermomyotome, and migrate into the limb bud, where they proliferate, express myogenic determination factors and subsequently differentiate into skeletal muscle. A number of regulatory factors involved in these different steps have been identified. These include Pax3 with its target c-met, Lbx1 and Mox2 as well as the myogenic determination factors Myf5 and MyoD and factors required for differentiation such as Myogenin, Mrf4 and Mef2 isoforms. Mutants for genes such as Lbx1 and Mox2, expressed uniformly in limb muscle progenitors, reveal unexpected differences between fore and hind limb muscles, also indicated by the differential expression of Tbx genes. As development proceeds, a secondary wave of myogenesis takes place, and, postnatally, satellite cells become located under the basal lamina of adult muscle fibres. Satellite cells are thought to be the progenitor cells for adult muscle regeneration, during which similar genes to those which regulate myogenesis in the embryo also play a role. In particular, Pax3 as well as its orthologue Pax7 are important. The origin of secondary/fetal myoblasts and of adult satellite cells is unclear, as is the relation of the latter to so-called SP or stem cell populations, or indeed to potential mesangioblast progenitors, present in blood vessels. The oligoclonal origin of postnatal muscles points to a small number of founder cells, whether or not these have additional origins to the progenitor cells of the somite which form the first skeletal muscles, as discussed here for the embryonic limb.

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Figures

Fig. 1
Fig. 1
Schematic representation of somitogenesis.
Fig. 2
Fig. 2
Mouse embryos at embryonic day (E) E10.5 with one (A–C) or two (D–F) alleles of Pax3 targeted with an nlacZ reporter sequence. In heterozygote embryos (A–C), β-galactosidase (Pax3)-positive cells can be seen in the forelimb bud (A and B, black arrow). At the hindlimb bud level (A and C), at this stage, β-galactosidase-positive (Pax3) cells delaminating from the somites and beginning to migrate are seen (blue arrow). In homozygote Pax3 mutant embryos (D–F) there is characteristic spinal bifidia and exencephaly. The dermomyotome of the somites is severely reduced (D). The forelimb (E) has no labelled (Pax3-positive) cells (black arrow). At the hindlimb level (F), there is also no sign of migrating cells (blue arrow).
Fig. 3
Fig. 3
Schematic representation of skeletal muscle formation in the limb, with the different stages and genes potentially involved at each stage. NC, notochord; NT, neural tube; SE, surface ectoderm.
Fig. 4
Fig. 4
Myogenic genes expressed in adult muscle satellite cells. (A) Dapi staining of nuclei in an isolated adult muscle fibre. (B) The same fibre, showing a Pax3-positive satellite cell (from an nlacZ-targeted allele). (C) Dapi staining of nuclei in an isolated adult muscle fibre. (D) The same fibre showing two Myf5-positive satellite cells (from an nlacZ-targeted Myf5 allele). (E) Dapi staining of nuclei in an isolated adult muscle fibre. (F) The same fibre showing Pax3-positive (β-Gal) satellite cells. (G) The same fibre showing that the same cells (see H) are expressing Pax7. (H) A merge of F and G. C and D are modified from Beauchamp et al. (2000).
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